PMID- 30155683 OWN - NLM STAT- MEDLINE DCOM- 20190220 LR - 20200225 IS - 1476-3524 (Electronic) IS - 1029-8428 (Print) IS - 1029-8428 (Linking) VI - 35 IP - 1 DP - 2019 Jan TI - Blebbistatin, a Myosin II Inhibitor, Exerts Antidepressant-Like Activity and Suppresses Detrusor Overactivity in an Animal Model of Depression Coexisting with Overactive Bladder. PG - 196-207 LID - 10.1007/s12640-018-9948-5 [doi] AB - Overactive bladder (OAB) coexists with depression in women. Here, we assessed the effects of a 1-week treatment with blebbistatin, a myosin II inhibitor, on changes in behavior and detrusor overactivity (DO) symptoms induced by a 6-week administration of 13-cis-retinoic acid (13-cis-RA), with the aid of the forced swim test (FST), spontaneous locomotor activity test, and in vivo cystometric investigations in female Wistar rats. 13-cis-RA-induced depressive-like behavior and DO symptoms were associated with increased corticotropin-releasing factor (CRF) level in the plasma, prefrontal cortex (PFC), hippocampus (Hp), Barrington's nucleus (BN), and urinary bladder. Moreover, 13-cis-RA decreased brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) levels in plasma, PFC, Hp, and BN, while it increased BDNF and NGF levels in urinary bladder. Blebbistatin exerted antidepressant-like effect and attenuated changes in the cystometric parameters as well as the central and peripheral levels of CRF, BDNF, and NGF that were induced by 13-cis-RA, while it did not affect urine production, mean, systolic or diastolic blood pressure, or heart rate. The results point to blebbistatin as a potential treatment option for OAB coexisting with depression. FAU - Wrobel, Andrzej AU - Wrobel A AD - Second Department of Gynecology, Medical University of Lublin, Jaczewskiego 8, 20-090, Lublin, Poland. wrobelandrzej@yahoo.com. FAU - Doboszewska, Urszula AU - Doboszewska U AD - Department of Animal Physiology, Institute of Biology and Biochemistry, Faculty of Biology and Biotechnology, Maria Curie-Sklodowska University, Akademicka 19, 20-033, Lublin, Poland. urszula.doboszewska@umcs.lublin.pl. FAU - Rechberger, Ewa AU - Rechberger E AD - Second Department of Gynecology, Medical University of Lublin, Jaczewskiego 8, 20-090, Lublin, Poland. FAU - Banczerowska-Gorska, Malgorzata AU - Banczerowska-Gorska M AD - Gynaecological and Obstetrics Hospital in Walbrzych, Paderewskiego 10, 58-301, Walbrzych, Poland. FAU - Czuczwar, Piotr AU - Czuczwar P AD - Third Department of Gynecology, Medical University of Lublin, Jaczewskiego 8, 20-954, Lublin, Poland. FAU - Poleszak, Ewa AU - Poleszak E AD - Chair and Department of Applied Pharmacy, Medical University of Lublin, Chodzki 1, 20-093, Lublin, Poland. FAU - Dudka, Jaroslaw AU - Dudka J AD - Chair and Department of Toxicology, Medical University of Lublin, Chodzki 8, 20-093, Lublin, Poland. FAU - Wlaz, Piotr AU - Wlaz P AD - Department of Animal Physiology, Institute of Biology and Biochemistry, Faculty of Biology and Biotechnology, Maria Curie-Sklodowska University, Akademicka 19, 20-033, Lublin, Poland. FAU - Miotla, Pawel AU - Miotla P AD - Second Department of Gynecology, Medical University of Lublin, Jaczewskiego 8, 20-090, Lublin, Poland. FAU - Wlazlak, Edyta AU - Wlazlak E AD - Clinic of Operative Gynecology and Gynecologic Oncology, 1st Department of Gynecology and Obstetrics, Medical University of Lodz, Wilenska 37, 94-029, Lodz, Poland. FAU - Rechberger, Tomasz AU - Rechberger T AD - Second Department of Gynecology, Medical University of Lublin, Jaczewskiego 8, 20-090, Lublin, Poland. LA - eng PT - Journal Article DEP - 20180828 PL - United States TA - Neurotox Res JT - Neurotoxicity research JID - 100929017 RN - 0 (Antidepressive Agents) RN - 0 (Autonomic Agents) RN - 0 (Bdnf protein, rat) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Heterocyclic Compounds, 4 or More Rings) RN - 20WC4J7CQ6 (blebbistatin) RN - 9015-71-8 (Corticotropin-Releasing Hormone) RN - 9061-61-4 (Nerve Growth Factor) RN - EC 3.6.1.- (Myosin Type II) RN - EH28UP18IF (Isotretinoin) SB - IM MH - Animals MH - Antidepressive Agents/*pharmacology MH - Autonomic Agents/*pharmacology MH - Brain/metabolism MH - Brain-Derived Neurotrophic Factor/metabolism MH - Corticotropin-Releasing Hormone/metabolism MH - Depression/complications/*drug therapy MH - Disease Models, Animal MH - Female MH - Heterocyclic Compounds, 4 or More Rings/*pharmacology MH - Isotretinoin MH - Myosin Type II/antagonists & inhibitors/metabolism MH - Nerve Growth Factor/metabolism MH - Random Allocation MH - Rats, Wistar MH - Urinary Bladder/*drug effects/physiopathology MH - Urinary Bladder, Overactive/complications/*drug therapy PMC - PMC6313360 OTO - NOTNLM OT - 13-cis-Retinoic acid OT - Blebbistatin OT - Forced swim test OT - Overactive bladder OT - Rats COIS- The authors declare that they have no conflict of interest. EDAT- 2018/08/30 06:00 MHDA- 2019/03/21 06:00 PMCR- 2018/08/28 CRDT- 2018/08/30 06:00 PHST- 2018/06/06 00:00 [received] PHST- 2018/08/15 00:00 [accepted] PHST- 2018/08/13 00:00 [revised] PHST- 2018/08/30 06:00 [pubmed] PHST- 2019/03/21 06:00 [medline] PHST- 2018/08/30 06:00 [entrez] PHST- 2018/08/28 00:00 [pmc-release] AID - 10.1007/s12640-018-9948-5 [pii] AID - 9948 [pii] AID - 10.1007/s12640-018-9948-5 [doi] PST - ppublish SO - Neurotox Res. 2019 Jan;35(1):196-207. doi: 10.1007/s12640-018-9948-5. Epub 2018 Aug 28.